PB2186: MOLECULAR RESPONSE TO INTERFERON IN PREFIBROTIC PRIMARY MYELOFIBROSIS- RETROSPECTIVE SINGLE CENTER STUDY
Authors: Emine Kaynak, Veronika Sygulla, Otto Zach, Gerald Webersinke, Mathilde Foedermayr-Mayrleitner, Christine Gruber, Wolfgang Schimetta, Johannes Clausen, Irene Strassl, Olga Stiefel, Sigrid Machherndl-Spandl, Margarete Moyses, Michael Girschikofsky, Andreas Petzer, Veronika Buxhofer-Ausch
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Interferon is a well-known therapy for a long time in early stage myeloproliferative neoplasms; its good efficacy and potential disease modifying effect is very much appreciated (Bewersdorf et al, Leukemia 2021). However, there is little data on efficacy in prePMF, a relatively newly defined subentity of MPN. Aims: We conducted a retrospective single center study in a cohort of WHO classified prePMF patients to investigate the hematological and molecular response and determine factors that influence response to interferon. Methods: Inclusion requested a diagnosis according to WHO and either a JAK2V617F or a Calreticulin (CALR) mutation. Clinical and molecular responses were calculated after 6 and 12 months, both in the whole cohort and also separately in the 2 molecular subtypes. Multiple linear regression analyses investigated the influence of several co-variables on hematological and molecular response parameters. Results: We included 29 patients with a median time on interferon of 35.9 months. In nearly 90% of patients a normalization of white blood cell count (WBC) was achieved, while a normal platelet count occurred in 65% of patients on interferon. Regarding the molecular response after 6 months, 20.69%/10.34% of patients showed a >25%/ >50% reduction of the allele burden, which almost doubled after 12 months (40%/16%). Both, in the entire cohort as well as in the 2 molecular subgroups separately, multivariate analysis did not reveal any substantial influence of the investigated variables on the molecular response. In the entire cohort, a lower allele burden correlated clearly with less WBC (p= 0.011) and PLT (p= 0.032) response after 6 months. Subgroup analysis indicates that the correlation of allele burden with WBC and PLT response might be confined to the CALR mutated patients. Younger age and detectable fibrosis were associated with less LDH response after 6 months (p= 0.040 for age and 0.034 for fibrosis, respectively) as well as 12 months (p= 0.04 for age and p= 0.084 for fibrosis, respectively). Regarding the JAK2 mutated subgroup separately, the presence of non-driver mutations was related to less PLT reduction (p= 0.046) and younger age to less LDH response (p= 0.048) after 12 months on interferon. Summary/Conclusion: The study revealed substantial molecular responses already 6 months after start with interferon which doubled after 12 months. Molecular responses appear to be independent of various clinical and molecular parameters. Molecular subgroup analyses suggest a difference in the influence of certain parameters on treatment response. Enlargement of the patient cohort and reanalysis after longer follow-up are planned. Literature: Bewersdorf JP et al. Interferon alpha therapy in essential thrombocythemia and polycythemia vera-a systematic review and meta-analysis. Leukemia. 2021 Jun;35(6):1643-1660. doi: 10.1038/s41375-020-01020-4. Epub 2020 Sep 1. PMID: 32868875; PMCID: PMC7917159. Keywords: Myelofibrosis, Interferon alpha